Details for: DAPK2

Gene ID: 23604

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: DAPK2

Ensembl ID: ENSG00000035664

Description: death associated protein kinase 2

Cell Significance Landscape

Associated with

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • cardiac muscle cell CL0000746
    CSI 25.52
    rCSI 36.62%
    PRS 71.86
  • regular atrial cardiac myocyte CL0002129
    CSI 12.13
    rCSI 39.05%
    PRS 78.64
  • chondrocyte CL0000138
    CSI 11.49
    rCSI 18.27%
    PRS 75.2
  • renal interstitial pericyte CL1001318
    CSI 9.58
    rCSI 26.39%
    PRS 77.22
  • brush cell of tracheobronchial tree CL0002075
    CSI 6.69
    rCSI 19.84%
    PRS 89.69
  • epithelial cell of lower respiratory tract CL0002632
    CSI 5.46
    rCSI 4.23%
    PRS 85.42
  • fibroblast of lung CL0002553
    CSI 4.91
    rCSI 4.57%
    PRS 82.62
  • granulocyte CL0000094
    CSI 4.75
    rCSI 7.26%
    PRS 88.3
  • BEST4+ enteroycte CL4030026
    CSI 4.13
    rCSI 5.13%
    PRS 82.53
  • adipocyte CL0000136
    CSI 3.75
    rCSI 4.82%
    PRS 72.27
  • subcutaneous adipocyte CL0002521
    CSI 3.15
    rCSI 16.13%
    PRS 84.64
  • goblet cell CL0000160
    CSI 3.06
    rCSI 2.89%
    PRS 80.23
  • endocardial cell CL0002350
    CSI 3
    rCSI 14.35%
    PRS 78.29
  • intestine goblet cell CL0019031
    CSI 2.95
    rCSI 2.61%
    PRS 79.63
  • epithelial cell of lung CL0000082
    CSI 2.93
    rCSI 2.43%
    PRS 82.69
  • transit amplifying cell of colon CL0009011
    CSI 2.91
    rCSI 3.42%
    PRS 83.3
  • colon epithelial cell CL0011108
    CSI 2.68
    rCSI 2.81%
    PRS 79.25
  • cardiac endothelial cell CL0010008
    CSI 2.66
    rCSI 10.72%
    PRS 81.83
  • CD8-positive, alpha-beta memory T cell CL0000909
    CSI 2.65
    rCSI 2.77%
    PRS 92.83
  • lamp5 GABAergic cortical interneuron CL4023011
    CSI 2.63
    rCSI 4.41%
    PRS 64.4
  • type L enteroendocrine cell CL0002279
    CSI 2.61
    rCSI 4.9%
    PRS 87.93
  • blood vessel endothelial cell CL0000071
    CSI 2.47
    rCSI 5.12%
    PRS 78.7
  • pancreatic A cell CL0000171
    CSI 2.45
    rCSI 2.57%
    PRS 84.81
  • conjunctival epithelial cell CL1000432
    CSI 2.42
    rCSI 3.7%
    PRS 81.85
  • pulmonary alveolar type 1 cell CL0002062
    CSI 2.21
    rCSI 12.73%
    PRS 78.28
  • L2/3-6 intratelencephalic projecting glutamatergic neuron CL4023040
    CSI 2.19
    rCSI 5.33%
    PRS 62.34
  • cardiac neuron CL0010022
    CSI 2.15
    rCSI 6.88%
    PRS 79.37
  • myoepithelial cell CL0000185
    CSI 2.12
    rCSI 5.35%
    PRS 86.37
  • M cell of gut CL0000682
    CSI 2.03
    rCSI 2.16%
    PRS 86.24
  • renal beta-intercalated cell CL0002201
    CSI 2.03
    rCSI 4.83%
    PRS 81.86
  • pulmonary alveolar type 2 cell CL0002063
    CSI 1.99
    rCSI 3.09%
    PRS 85.2
  • colonocyte CL1000347
    CSI 1.83
    rCSI 2.62%
    PRS 82.08
  • pancreatic acinar cell CL0002064
    CSI 1.79
    rCSI 2.38%
    PRS 86.83
  • retinal ganglion cell CL0000740
    CSI 1.75
    rCSI 3.87%
    PRS 68.03
  • foveolar cell of stomach CL0002179
    CSI 1.71
    rCSI 3.63%
    PRS 87.26
  • epicardial adipocyte CL1000309
    CSI 1.71
    rCSI 5.55%
    PRS 79.62
  • enteroendocrine cell of small intestine CL0009006
    CSI 1.69
    rCSI 3.72%
    PRS 88.53
  • fast muscle cell CL0000190
    CSI 1.65
    rCSI 6.44%
    PRS 77.82
  • endothelial cell of vascular tree CL0002139
    CSI 1.64
    rCSI 8.95%
    PRS 78.25
  • paneth cell of epithelium of small intestine CL1000343
    CSI 1.53
    rCSI 4.3%
    PRS 87.93
  • lung resident memory CD8-positive, alpha-beta T cell CL4033039
    CSI 1.53
    rCSI 3.96%
    PRS 95.14
  • mesangial cell CL0000650
    CSI 1.46
    rCSI 5.96%
    PRS 89.72
  • lung secretory cell CL1000272
    CSI 1.46
    rCSI 3.6%
    PRS 81.88
  • basal cell of epidermis CL0002187
    CSI 1.42
    rCSI 2.52%
    PRS 50.88
  • effector CD4-positive, alpha-beta T cell CL0001044
    CSI 1.38
    rCSI 3.97%
    PRS 95.69
  • small intestine goblet cell CL1000495
    CSI 1.35
    rCSI 2.96%
    PRS 86.65
  • intestinal crypt stem cell of small intestine CL0009017
    CSI 1.33
    rCSI 3.6%
    PRS 85.91
  • CD8-positive, CD28-negative, alpha-beta regulatory T cell CL0000920
    CSI 1.3
    rCSI 2.58%
    PRS 92.03
  • transit amplifying cell of small intestine CL0009012
    CSI 1.04
    rCSI 4.58%
    PRS 88.68
  • near-projecting glutamatergic cortical neuron CL4023012
    CSI 0.92
    rCSI 3.48%
    PRS 64.95
  • type EC enteroendocrine cell CL0000577
    CSI 0.83
    rCSI 2.94%
    PRS 85.48
  • regular ventricular cardiac myocyte CL0002131
    CSI 0.81
    rCSI 5.06%
    PRS 73.75
  • luminal cell of prostate epithelium CL0002340
    CSI 0.66
    rCSI 3.55%
    PRS 88.62
  • enterocyte of epithelium of small intestine CL1000334
    CSI 0.33
    rCSI 5.12%
    PRS 88.74

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

Explore relationships of the current gene. Select an Interaction Source: 'ONTOLOGY' for shared pathways (GO/Reactome) or 'STRING' for protein-protein interactions. Further refine by selecting context genes and comparing Cell Significance Index (CSI) scores between baseline and target cell types and their specific contexts.

Comma-separated if multiple.
Comma-separated if multiple.
Legend:
  • Query Gene
  • Node Color (Target Cell CSI, relative to current network):
    • Very High
    • High
    • Medium
    • Low
    • Very Low
    • CSI N/A
  • Node Size: Proportional to Target Cell CSI magnitude
  • STRING PPI Edge
  • Shared Pathway Edge (ONTOLOGY)

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Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary [DAPK2](/details-gene/23604) (Death-Associated Protein Kinase 2) is a protein-coding gene located on chromosome 15 that encodes a calcium/calmodulin-dependent serine/threonine kinase. As a member of the DAP-kinase family, it is a key regulator of programmed cell death, involved in signaling pathways that lead to apoptosis and autophagy ([Link](https://doi.org/10.1038/sj.onc.1202701), [Link](https://doi.org/10.1083/jcb.200109094)). **Overall**, expression data reveals its highest significance in [cardiac muscle cell](/details-cell/CL0000746)s, suggesting a potentially critical role in cardiac homeostasis. It is also notably active in other structural cells like [chondrocyte](/details-cell/CL0000138)s and in myeloid immune cells such as [granulocyte](/details-cell/CL0000094), where it has been shown to regulate cell maturation and chemotaxis ([Link](https://doi.org/10.1189/jlb.0606400)). ## Cellular Roles and Expression Landscape The expression profile of [DAPK2](/details-gene/23604) highlights a dual role in both structural tissues and the immune system. **Overall**, the gene's most prominent significance is observed in contractile and structural cell types. It is an exceptionally strong marker for [cardiac muscle cell](/details-cell/CL0000746) (CSI: 25.52) and its subtype, the [regular atrial cardiac myocyte](/details-cell/CL0002129) (CSI: 12.13), as well as [chondrocyte](/details-cell/CL0000138) (CSI: 11.49) and [renal interstitial pericyte](/details-cell/CL1001318) (CSI: 9.58). This pattern suggests a role for [DAPK2](/details-gene/23604) in the regulation of cellular stress, turnover, or programmed cell death within these specialized, long-lived cell populations. Concurrently, [DAPK2](/details-gene/23604) demonstrates significant expression in various epithelial and immune cells. Its presence in [granulocyte](/details-cell/CL0000094) (CSI: 4.75) is consistent with published research indicating its function in enhancing neutrophil maturation and positively regulating both neutrophil and eosinophil chemotaxis ([Link](https://doi.org/10.1189/jlb.0606400), [Link](https://doi.org/10.1189/jlb.0813462)). Its expression in secretory cells like [goblet cell](/details-cell/CL0000160) and various respiratory and intestinal epithelial cells further suggests a broader role in tissue maintenance and response to stimuli across different organ systems. ## Pathways and Molecular Function The molecular functions of [DAPK2](/details-gene/23604) are centered on its protein serine/threonine kinase activity ([GO:0004674](https://www.ebi.ac.uk/QuickGO/term/GO:0004674)), which is dependent on ATP ([GO:0005524](https://www.ebi.ac.uk/QuickGO/term/GO:0005524)) and calmodulin binding ([GO:0005516](https://www.ebi.ac.uk/QuickGO/term/GO:0005516)). Its catalytic activity is a key driver of its biological roles, which primarily involve the regulation of cell death and motility. Functionally, [DAPK2](/details-gene/23604) is a well-established component of the cellular machinery for programmed cell death. It is annotated in pathways for [Apoptosis](/details-pathway/R-HSA-109581) ([R-HSA-109581](https://reactome.org/content/detail/R-HSA-109581)) and is a positive regulator of the apoptotic process ([GO:0043065](https://www.ebi.ac.uk/QuickGO/term/GO:0043065)). This includes involvement in anoikis, a form of apoptosis induced by cell-detachment ([GO:0043276](https://www.ebi.ac.uk/QuickGO/term/GO:0043276)), and the regulation of autophagy ([GO:0010506](https://www.ebi.ac.uk/QuickGO/term/GO:0010506)). Furthermore, its established role in the positive regulation of [eosinophil chemotaxis](/details-goprocess/GO:2000424) ([GO:2000424](https://www.ebi.ac.uk/QuickGO/term/GO:2000424)) and [neutrophil chemotaxis](/details-goprocess/GO:0090023) ([GO:0090023](https://www.ebi.ac.uk/QuickGO/term/GO:0090023)) directly links its kinase activity to the functional responses of granulocytes, which aligns with its observed expression in these cells. ## Research Directions The striking contrast between the well-documented role of [DAPK2](/details-gene/23604) in apoptosis and immunity and its uniquely high expression in [cardiac muscle cell](/details-cell/CL0000746)s presents intriguing avenues for future research. This suggests that its primary function may be highly context-dependent, shifting from immune modulation to homeostatic cell turnover in terminally differentiated tissues. Based on the available data, several testable hypotheses can be proposed: 1. The high expression of [DAPK2](/details-gene/23604) in [cardiac muscle cell](/details-cell/CL0000746)s is essential for mediating programmed cell death in response to pathological stress, such as ischemia or pressure overload. Dysregulation of [DAPK2](/details-gene/23604) activity may therefore be a contributing factor to the progression of heart failure. 2. In myeloid cells like [granulocyte](/details-cell/CL0000094)s, [DAPK2](/details-gene/23604) functions as a signaling hub that integrates chemoattractant receptor signals with the cytoskeletal changes required for cell migration. Its activity may be acutely modulated by phosphorylation or protein-protein interactions during an inflammatory response. To test the first hypothesis regarding its cardiac role, a compelling experimental approach would be to utilize a conditional knockout mouse model. By crossing mice with floxed *Dapk2* alleles to a line expressing Cre recombinase under a cardiac-specific promoter (e.g., *Myh6*-Cre), one could specifically ablate [DAPK2](/details-gene/23604) in cardiomyocytes. These conditional knockout mice and their wild-type littermates could then be subjected to a model of cardiac injury, such as transverse aortic constriction (TAC) or myocardial infarction. The subsequent impact on cardiac function (via echocardiography), fibrosis (via histology), and cardiomyocyte apoptosis (via TUNEL staining) would directly elucidate the in vivo role of [DAPK2](/details-gene/23604) in cardiac pathophysiology. As a druggable serine/threonine kinase, [DAPK2](/details-gene/23604) holds therapeutic potential. Its pro-apoptotic function suggests that small-molecule activators of [DAPK2](/details-gene/23604) could be investigated as a strategy to re-sensitize cancer cells to apoptosis, particularly in malignancies where its expression or function is suppressed ([Link](https://doi.org/10.1074/jbc.m805612200)). Conversely, given its high expression in the heart, selective inhibitors of [DAPK2](/details-gene/23604) could represent a novel therapeutic approach to limit cardiomyocyte death and adverse remodeling following ischemic events like a heart attack.

Genular Protein ID: 2779257765

Symbol: DAPK2_HUMAN

Name: Death-associated protein kinase 2

UniProtKB Accession Codes:

Q9UIK4 E9JGM7 O75892 Q24JS1

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BindingDB 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 2 CDD 1 CTD 1 ChEBI 13 ChEMBL 1 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 DrugBank 1 DrugCentral 1 EC 2 EMBL 6 Ensembl 4 EvolutionaryTrace 1 ExpressionAtlas 1 GO 22 Gene3D 2 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 4 KEGG 1 MANE-Select 1 MIM 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PDB 11 PDBsum 11 PRO 1 PROSITE 3 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 3 RNAct 1 Reactome 1 RefSeq 2 Rhea 6 SIGNOR 1 SMART 1 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 10376525

Title: Death-associated protein kinase 2 is a new calcium/calmodulin-dependent protein kinase that signals apoptosis through its catalytic activity.

PubMed ID: 10376525

DOI: 10.1038/sj.onc.1202701

PubMed ID: 10629061

Title: Death-associated protein kinase-related protein 1, a novel serine/threonine kinase involved in apoptosis.

PubMed ID: 10629061

DOI: 10.1128/mcb.20.3.1044-1054.2000

PubMed ID: 21408167

Title: New modularity of DAP-kinases: alternative splicing of the DRP-1 gene produces a ZIPk-like isoform.

PubMed ID: 21408167

DOI: 10.1371/journal.pone.0017344

PubMed ID: 16572171

Title: Analysis of the DNA sequence and duplication history of human chromosome 15.

PubMed ID: 16572171

DOI: 10.1038/nature04601

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

PubMed ID: 11230133

Title: Autophosphorylation restrains the apoptotic activity of DRP-1 kinase by controlling dimerization and calmodulin binding.

PubMed ID: 11230133

DOI: 10.1093/emboj/20.5.1099

PubMed ID: 12445458

Title: The DAP-kinase family of proteins: study of a novel group of calcium-regulated death-promoting kinases.

PubMed ID: 12445458

DOI: 10.1016/s1570-9639(02)00443-0

PubMed ID: 11980920

Title: DAP kinase and DRP-1 mediate membrane blebbing and the formation of autophagic vesicles during programmed cell death.

PubMed ID: 11980920

DOI: 10.1083/jcb.200109094

PubMed ID: 16756490

Title: The death-associated protein kinases: structure, function, and beyond.

PubMed ID: 16756490

DOI: 10.1146/annurev.biochem.75.103004.142615

PubMed ID: 17347302

Title: The death-associated protein kinase 2 is up-regulated during normal myeloid differentiation and enhances neutrophil maturation in myeloid leukemic cells.

PubMed ID: 17347302

DOI: 10.1189/jlb.0606400

PubMed ID: 18669648

Title: A quantitative atlas of mitotic phosphorylation.

PubMed ID: 18669648

DOI: 10.1073/pnas.0805139105

PubMed ID: 18957423

Title: Down-regulation of death-associated protein kinase-2 is required for beta-catenin-induced anoikis resistance of malignant epithelial cells.

PubMed ID: 18957423

DOI: 10.1074/jbc.m805612200

PubMed ID: 23186163

Title: Toward a comprehensive characterization of a human cancer cell phosphoproteome.

PubMed ID: 23186163

DOI: 10.1021/pr300630k

PubMed ID: 24163421

Title: DAPK2 positively regulates motility of neutrophils and eosinophils in response to intermediary chemoattractants.

PubMed ID: 24163421

DOI: 10.1189/jlb.0813462

PubMed ID: 26047703

Title: Suppression of death-associated protein kinase 2 by interaction with 14-3-3 proteins.

PubMed ID: 26047703

DOI: 10.1016/j.bbrc.2015.05.105

PubMed ID: 17344846

Title: Patterns of somatic mutation in human cancer genomes.

PubMed ID: 17344846

DOI: 10.1038/nature05610

Sequence Information:

  • Length: 370
  • Mass: 42898
  • Checksum: 035E914BBCD881A2
  • Sequence:
    • MFQASMRSPN MEPFKQQKVE DFYDIGEELG SGQFAIVKKC REKSTGLEYA AKFIKKRQSR 
ASRRGVSREE IEREVSILRQ VLHHNVITLH DVYENRTDVV LILELVSGGE LFDFLAQKES 
LSEEEATSFI KQILDGVNYL HTKKIAHFDL KPENIMLLDK NIPIPHIKLI DFGLAHEIED 
GVEFKNIFGT PEFVAPEIVN YEPLGLEADM WSIGVITYIL LSGASPFLGD TKQETLANIT 
AVSYDFDEEF FSQTSELAKD FIRKLLVKET RKRLTIQEAL RHPWITPVDN QQAMVRRESV 
VNLENFRKQY VRRRWKLSFS IVSLCNHLTR SLMKKVHLRP DEDLRNCESD TEEDIARRKA 
LHPRRRSSTS